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Daws, Lynette C.; Callaghan, Paul D.; Morón, José A.; Kahlig, Kris M.; Shippenberg, Toni S.; Javitch, Jonathan A.; Galli, Aurelio
In HEK 293 cells expressing the human dopamine transporter (DAT), a 10-min incubation with 10 μM cocaine followed by extensive washing resulted in a 30% increase in ( 3 H)dopamine (DA) uptake as well as an increase in cell surface DAT in biotinylation experiments. Consistent with this novel regulation, ( 3 H)DA uptake into synaptosomes prepared from the nucleus accumbens of rats sacrificed 30 min after a single cocaine injection (30 mg/kg) was significantly increased compared to controls (56% increase in V max , no change in K m ). In addition, DA clearance in the striatum of anesthetized rats was increased after local application of a low (3 pmol) but not high (65 pmol) dose of cocaine, presumably as a result of mobilization of DAT to the cell surface. Cocaine-induced increases in cell surface expression of DAT and associated changes in DA clearance represent a novel mechanism that may play a role in its addictive properties.
http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.pngBiochemical and Biophysical Research CommunicationsElsevierhttp://www.deepdyve.com/lp/elsevier/cocaine-increases-dopamine-uptake-and-cell-surface-expression-of-U0bwflKP5v